Chronic Graft-versus-host-disease
Conditions
Keywords
cGVHD
Brief summary
This study will be conducted to determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with cGVHD.
Interventions
DRUGAxatilimab
Axatilimab will be administered at protocol defined dose.
DRUGRuxolitinib
Ruxolitinib will be administered at protocol defined dose.
DRUGCorticosteroids
Corticosteroids will be administered at protocol defined dose.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 12 years of age at the time of informed consent. * New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy. * History of 1 allo-SCT (any type of stem cell donor, any conditioning regimen, and source of hematopoietic stem cells). * Adequate hematologic function independent of platelet transfusion and growth factors for at least 7 days prior to study entry: ANC ≥ 0.75 × 109/L and platelet count ≥ 20 × 109/L. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* Received more than 1 prior allo-SCT. Prior autologous HCT is allowed. * Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD. * Received previous systemic treatment for cGVHD, including systemic corticosteroids and extracorporeal photopheresis. * Received systemic corticosteroids within 2 weeks prior to C1D1, regardless of indication. * Initiated systemic treatment with CNIs or mTOR inhibitors within 2 weeks prior to C1D1. * Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for the treatment of aGVHD are eligible only if they achieved a response (CR or PR) to JAK inhibitor treatment and did not discontinue due to toxicity. * Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-SCT was performed, including DLIs for the treatment of molecular relapse. * History of acute or chronic pancreatitis. * History of thromboembolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) in the 6 months prior to study entry. * Active symptomatic myositis. * Severe renal impairment, that is, estimated CrCl \< 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or end-stage renal disease on dialysis. Participants with CrCl of 30 to 59 mL/min on treatment with fluconazole are not eligible. * Impaired liver function, defined as total bilirubin \> 1.5 × ULN and/or ALT and AST \> 3 × ULN in participants with no evidence of liver cGVHD. * Currently active significant cardiac disease, such as uncontrolled arrhythmias, uncontrolled hypertension, or Class 3 or 4 congestive heart failure as defined by New York Heart Association, or a history of myocardial infarction or unstable angina within 6 months prior to randomization. * Pregnant or breastfeeding. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 6 months | Defined as Complete Response (CR) or Partial Response (PR) at 6 months in the absence of new systemic therapy for cGVHD. Response assessment will be based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | Up to 2 years and 30 days | Defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment. |
| Duration of Response | Up to 2 years | Defined as the time from the first response (PR or CR) to the date of progression of cGVHD, start of new systemic therapy or death from any cause. |
| Proportion of participants with a ≥ 7-point improvement in modified Lee symptom scale (mLSS) score | Up to 2 years | — |
| Best overall response in the first 6 months | Up to 6 months | Define as PR or CR in the first 6 months. |
| OR at 12 months, defined as CR or PR at 12 months (C14D1) in the absence of new systemic therapy for cGVHD. | 12 months | Defined as CR or PR at 12 months in the absence of new systemic therapy for cGVHD |
| Proportion of participants who remain corticosteroid-free | 4 weeks, 8 weeks and 6 months | — |
| Organ-specific response in the first 6 cycles and on study, based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD. | Up to 2 years | Based on the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD. |
| Failure-free Survival (FFS) | Up to 2 years and 30 days | Defined as the time from date of randomization to date of initiation of a new cGVHD treatment, malignancy relapse, or death due to any cause. |
| Axatilimab pharmacokinetic (PK) in Plasma | Up to 2 years and 30 days | Axatilimab concentration in plasma. |
| Ruxolitinib PK in Plasma | Up to 2 years and 30 days | Ruxolitinib concentration in plasma. |
Countries
Belgium, Canada, Germany, Italy, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed